Infectious Bursal Disease, also called "Gumboro Disease," is an acute and highly contagious viral infection of young chickens and other fowl. It is caused by Infectious Bursal Disease Virus (IBDV) Type I. The disease is characterized by degeneration of lymphoid tissue. The primary target of infection is the bursa of Fabricius, although lymphoid damage may also occur in the spleen, thymus, and gland of Harder.
Degeneration of the bursa of Fabricius and other lymphoid tissue in young chickens has severe economic consequences, as the infected chickens have a decreased response to vaccination and an increased susceptibility to other infectious agents.
Immunization is the principal method for controlling the disease. Chickens may be passively immunized, by receiving maternally-derived antibodies, or they may be actively immunized with live (attenuated) or killed (inactivated) vaccines. Live vaccines contain the virus that has been "modified" or attenuated through serial passaging in cell culture. By passaging it is hoped to produce a virus strain that is less pathogenic. In order to be useful in a vaccine, however, it must retain the antigenic and immunogenic properties of the original virus. It must, that is, induce the production of neutralizing antibodies. Control of the disease by immunization had been largely successful until variant strains began to emerge as the result of antigenic drift under field conditions. These variants were causing disease in both actively and passively immunized chickens.
Infectious Bursal Disease Virus is separately classified as Standard, Delaware and GLS. These strains can be characterized using a panel of monoclonal antibodies. The Delaware strain, which is divided into variants A-F, may be the most common IBDV presently found in the United States because existing vaccines have not provided adequate protection against these variants. We have developed a live "variant vaccine" using our novel virus strain 89-03 that will immunize young chickens against the Standard, the Delaware and the GLS variants.
In 1985, Dr. Rosenberger and researchers at the University of Delaware (Rosenberger et al., Isolation and Characterization of Variant Infectious Bursal Disease Viruses, Abstr 123rd Am. Vet. Med. Assoc. Meet., p. 357 (1986), isolated variants for which the Standard (ST) type IBD vaccines did not provide satisfactory protection. These variants became known as the Delaware variants. With immunochemical techniques, it was demonstrated by Snyder et al. (Snyder et al. Avian Diseases 32, pp 535-539, (1988) that the Delaware variants were true IBD variant viruses. Using the antigen capture ELISA (AC ELISA) test and monoclonal antibodies R63 and B69, which are directed against different epitopes of Standard IBDV, it was shown that the Delaware variants did not react with B69 monoclonal antibodies and, therefore, had lost their B69 epitope.
In 1989 Dr. Snyder and his coworkers isolated a virulent variant IBDV strain that had lost not only the B69 epitope but also the R63 epitope. This strain is known as GLS.
A large panel of monoclonal antibodies against IBDV Standard and variant strains was prepared by Dr. Snyder at the University of Maryland. Some of the monoclonal antibodies recognize only specific IBDV's. For example, monoclonal antibodies 67 and BK9 are specific for Delaware IBDV variants, whereas 57 is specific for GLS (Table 1).
TABLE 1 ______________________________________ Typing IBDV by Antigen Capture ELISA Monoclonal Anytibody* Virus Type 8 R63 B69 BK9 67 57 ______________________________________ Standard + + + - - - Delaware Variants + + - + + - GLS Variant + - - - - + ______________________________________ *All monoclonal antibodies obtained from Dr. David Snyder, University of Maryland, College Park, MD + Reacts with monoclonal antibody - Does not react with monoclonal antibody
Using a panel of different monoclonal antibodies, various IBDV types can be recognized. This has been shown to be a useful method to distinguish different IBDV strains.
When antigenic drift occurs and acceptable cross-protection with existing vaccines does not exist, new variant vaccines are required. Inactivated vaccines containing new variants are easier to develop than safe and effective live vaccines, but live vaccines are preferred.
Delaware variant E IBD field virus cannot be used in a live vaccine due to its pathogenicity. It must be attenuated by passaging in eggs or tissue culture to develop a safe live vaccine. Attenuation of Delaware strains in eggs or tissue culture has until the present invention always resulted in the loss of the specific Delaware variant immunological characteristics. Consequently, adapted/attenuated Delaware variant strains have not previously provided satisfactory protection against the homologous field variant strain. This was shown by Dr. Rosenberger, University of Delaware, Newark, Del. and co-workers (supra).
Dr. Rosenberger also showed that adaptation of Delaware variants on eggs or tissue culture decreased the immunogenicity when used in inactivated vaccines. Until now, the only way to prevent loss in antigenicity and/or immunogenicity of the Delaware variants was to grow the virus in the Bursa of Fabricius (Bursae derived antigens). The viral antigens could only be incorporated in inactivated vaccines due to the virulence and pathogenicity of bursal derived virus. To provide adequate protection against Delaware field infections, a live attenuated vaccine must induce the production of specific antibodies that recognize the field-type Delaware IBDV. That means, in the process of attenuation, the immunological characteristics of the Delaware virus must be retained, while pathogenicity and virulence must be reduced or eliminated.
The object of the present invention was to develop a new live vaccine by finding a Delaware E variant IBDV that retained Delaware type antigenicity without the pathogenicity of a field strain.
A further object of this invention was to develop a new and unique IBD virus vaccine strain that permits safe vaccination of all chickens and other fowl against all Standard, Delaware and GLS IBDV variants (Table 2).
TABLE 2 ______________________________________ Characterization of Different IBD Viruses by Monoclonal Antibodies 14 Monoclonal Antibody IBVD Vaccine/Virus 8 R63 B69 67 57 ______________________________________ Classical (USDA/ST).sup.1 + + + - - Delaware Variant E.sup.2 + + - + - Delaware Variant A.sup.2 + + - + - GLS Variant.sup.3 + - - - + 89/03 .TM..sup.4 + + - + - Primevac IBD-3 .TM..sup.4 + + + + + Maryland Strain.sup.3 + + + - - Clonevac D78 .RTM..sup.4 + + + - - Burcell 1+1 .RTM..sup.5 + + + - - Burcell 2+2 .RTM..sup.5 + + + - - Bursine .RTM..sup.6 + + + - - Bursine 2 .RTM..sup.6 + + + - - Melchior ATCC VR-2161.sup.10 + + + - - Sterwin 1084 E.sup.7 + + + - - Select S706 .RTM..sup.5 + + + - - Select SVS510 .RTM..sup.5 + + + - - Baxendale PBG-98.sup.4 + + + - - Bursavac .RTM..sup.7 + + + - - IBD Blen .RTM..sup.8 + + + - - ASL Variant IBD .RTM..sup.9 + + + - - ______________________________________ Tests carried out using AC ELISA + Reacts with monoclonal antibody - Does not react with monoclonal antibody .sup.1 Dr. Rebecca Hyde, USDA, National Veterinary Service Lab, Dayton Road, Ames, Iowa, 50010 .sup.2 Dr. John K. Rosenberger, University of Delaware, 040 Townsend Hall Newark, Delaware .sup.3 Dr. Dave Snyder, University of Maryland, AVRWM Guldesky Center, Room 1217, Vet Science Drive, College Park, Maryland 20742 .sup.4 Intervet Inc., 405 State Street, Millsboro, Delaware 19966 .sup.5 Select, P. O. Drawer 2497, Gainsville, Georgia .sup.6 Solvay (Salsbury Laboratories Inc.) Charles City, Iowa .sup.7 Sterwin Labs, Rt. 3, Box 537, Millsboro, Delaware 19966. Sterwin 1084 E is BursaVac .RTM.4. .sup.8 Sanofi, 7101 College Boulevard, Overland, Park, Kansas 66210 .sup.9 American Scientific Lab, Schering Corporation, Madison, Wisconsin 53707 .sup.10 American Type Culture Collection (ATCC) Rockville, Maryland